The etiology of childhood cancers is not well understood, and as such, the opportunities for prevention are few. Traffic-related air pollution is a possible human carcinogen, and constituents of are pollution such as benzene, 1,3-butadiene, and polycyclic aromatic hydrocarbons (PAHs) are established causes of human cancers. Evidence suggests that the fetus is more susceptible than the adult to a number of pollutants including PAHs and particulate matter. To date, however, there is only a small literature on air pollution and childhood cancers, and nearly all studies have utilized ecologic designs or simple proxies of air quality rather than relying on monitoring of criteria air pollutants or specific air toxics, or by utilizing sophisticated exposure models. Further, the rarity of childhood cancers have necessitated small sample sizes with few studies having adequate power to report risks for specific childhood cancer subtypes. In the proposed study, we wish to capitalize on the availability of widescale air monitoring of criteria air pollutants and the unique resource of community-based air toxics monitoring data to examine cancer risk among California children. Eligible subjects will include children age d5 in the California Cancer Registry (1988-2007, N=12042) and 10 controls per case selected at random from California birthrolls. Our specific aims are: (1) to estimate prenatal and early childhood exposures to air pollution using 4 metrics: existing measurement data from government operated monitoring stations;NOX and PM2.5 as estimated by CALINE4 air dispersion modeling;distance-weighted traffic density, which will be useful to compare results to previous studies;and specific air toxics (benzene, 1,3 butadiene, PAHs) using measurement data from existing community-based air monitoring stations;(2) to test the hypothesis that traffic-related air pollution increases risk of childhood cancer;(3) to test the hypothesis that general background air pollution increases cancer risk;(4) to test the hypothesis that certain air toxics increase risk of childhood cancers, with a particular focus on PAHs with brain and hematopoietic cancers;benzene with hematopoietic cancers;and 1,3 butadiene with hematopoietic cancers. Risks for the above pollutants will be generated based upon geocoded residential address, taken from birth certificates. The proposed study will be the largest to date to examine the cancer risks associated with air pollution and will utilize individual-level, refined and validated measures of vehicle exhaust related pollution concentrations. Importantly, we expect the findings to enhance our understanding of whether motor vehicle air toxics are the primary drivers of associations between childhood cancers and air pollutants observed in previous studies. If the proposed research is able to pinpoint specific toxins of greater relevance to birth outcomes, future research using personal and biomonitoring would be able to target these compounds. PUBLIC HEALTH RELEVANCE: Cancers are the second leading cause of death among children between infancy and age 15, with 10,730 new cases expected in the US in 2008. The etiology of childhood cancers is not well elucidated. The proposed study will examine perinatal and early life exposure to air pollution and test hypotheses of associations with later cancer development.